Interpretive Handbook

Test
87925 :
MAPT Gene, Sequence Analysis, Known Mutation

Frontotemporal dementia (FTLD) is a familial adult-onset, presenile dementia that affects the frontal and temporal cerebral cortices. Clinical presentation is variable and includes changes in behavior, difficulties with language, rigidity, palsy, and saccadic (rapid) eye movement. Symptoms generally begin between 40 and 60 years of age, with mean age of onset at approximately 45 years, and typically last between 5 and 10 years, progressing into severe dementia and mutism. The presentation of frontotemporal dementia may be confused with other dementias, including Alzheimer disease. It is important to distinguish between these different dementias because disease progression and patient management are different for the various dementias.

Based on the immunohistochemical staining, there are 2 main subtypes of FTLD: tau-positive FTLD and tau-negative FTLD with ubiquitin-positive inclusions (FTLD-U). Mutations in the MAPT gene have been identified in patients with tau-positive FTLD; mutations in the progranulin gene (GRN) have been identified in patients with FTLD-U. Both MAPT and GRN are located on chromosome 17q21.

The MAPT gene encodes the microtubule-associated tau protein. A number of mutations have been identified in the MAPT gene that result in aggregation of the tau protein. Although there is variable expression of disease presentation and severity within and between families, the hallmark neurologic lesion constitutes tau-positive protein inclusion bodies. Most clinically significant mutations are found in exons 9 through 13. Several intronic mutations, associated with alternative splicing of the mRNA, contribute to the variability of expression of the disease traits. Mutations in the MAPT gene have also been identified in cases of progressive supranuclear palsy, corticobasal degeneration, and dementia with epilepsy.

The identification of a disease-causing mutation in an affected family member is necessary before predictive testing for other family members can be offered. If a familial mutation has not been previously identified, order MAPTM / MAPT Gene, Sequence Analysis, 7 Exon Screening Panel.

Analysis is performed for the familial mutation(s) provided only. This assay does not rule out the presence of other mutations within this gene or within other genes that may be associated with frontotemporal dementia. This test can only be used for known mutations occurring in exons 1, 7, 9, 10, 11, 12, and 13 of the MAPT gene.

We strongly recommend that patients undergoing predictive testing receive genetic counseling both prior to testing and after results are available.

Predictive testing of an asymptomatic child is not recommended.

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Any error in the diagnosis or in the pedigree provided to us, including false-paternity, could lead to erroneous interpretation of results.

A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.